| Autor: |
Nameki, Robbin, Shetty, Anamay, Dareng, Eileen, Tyrer, Jonathan, Lin, Xianzhi, Ovarian Cancer Association Consortium, Pharoah, Paul, Corona, Rosario I, Kar, Siddhartha, Lawrenson, Kate |
| Přispěvatelé: |
Nameki, Robbin [0000-0002-2538-5694], Shetty, Anamay [0000-0003-0564-7236], Tyrer, Jonathan [0000-0003-3724-4757], Lawrenson, Kate [0000-0002-6469-2515], Apollo - University of Cambridge Repository |
| Rok vydání: |
2022 |
| Předmět: |
|
| DOI: |
10.17863/cam.87153 |
| Popis: |
Candidate causal risk variants from genome-wide association studies reside almost exclusively in noncoding regions of the genome and innovative approaches are necessary to understand their biological function. Multi-marker analysis of genomic annotation (MAGMA) is a widely used program that nominates candidate risk genes by mapping single-nucleotide polymorphism summary statistics from genome-wide association studies to gene bodies. We augmented MAGMA to create chromatin-MAGMA (chromMAGMA), a method to nominate candidate risk genes based on the presence of risk variants within noncoding regulatory elements (REs). We applied chromMAGMA to a genetic susceptibility dataset for epithelial ovarian cancer (EOC), a rare gynecologic malignancy characterized by high mortality. This identified 155 unique candidate EOC risk genes across five EOC histotypes; 83% (105/127) of high-grade serous ovarian cancer risk genes had not previously been implicated in this EOC histotype. Risk genes nominated by chromMAGMA converged on mRNA splicing and transcriptional dysregulation pathways. chromMAGMA is a pipeline that nominates candidate risk genes through a gene regulation-focused approach and helps interpret the biological mechanism of noncoding risk variants for complex diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
